The hypothesis to be tested in this project is that protein/protein interactions between the cytoplasmic domains of CD3 proteins and signalling molecules will initiate different pathways. Functional networking with other T cell activation molecules will be analyzed at each step. Specifically the following aims will be attempted. Generation of lymphocytes which are blocked in signal transduction through the TCR/CD3 Complex; determination of the role of tyrosine- and serine/threonine-phospho-kinases associated with the TCR/CD3 Complex; identification and isolation of guanine or adenosine nucleotide-binding proteins involved in T cell functions; isolation of proteins which have a propensity to associate with the intracellular domains of the CD3-gamma, delta, epsilon and zeta proteins.